A peripheral membrane protein is one that is attached to or embedded in a membrane, but does not span the membrane as does an integral membrane protein. The matrix protein vp40 from the Marburg virus is a peripheral membrane protein. It makes up about one-third of the virus particle and has similarities to the vp40 protein of the related Ebola virus. We have determined the three-dimensional structure of the Marburg vp40 protein. The protein has two domains and is found in the crystal in an oligomeric state that may reflect how it is packed into the viral particle. The protein functions as a dimer of two protein molecules bound together and we are able to detail the interactions that allow this binding. By analysis of the Marburg vp40 structure with comparison to the known Ebola structure, we hope to gain insights into the function of vp40 in virus replication and pathogenicity. Some 30% of all proteins known from genomic sequencing are predicted to be integral membrane proteins. But in contrast to the many structures of soluble proteins that are known, only a handful of membrane protein structures have been determined. We are working to crystallize and to determine structures of membrane proteins. We are trying to produce sufficient amounts for crystallization of a protein called the transporter associated with antigen processing (TAP). TAP actively transports small peptides from the cell's cytoplasm through the endoplasmic reticulum membrane where the peptides become bound to an antigen-presenting protein. T cells can respond to a peptide when it is bound to an antigen-presenting protein. Our approach is to produce the protein in bacteria as denatured polypeptide chains and then to renature the proteins to their native and functional conformations. After obtaining enough of the pure protein, we will crystallize the protein in preparation for an X-ray crystallographic structure determination.